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依布列xafungerp治疗血液系统恶性肿瘤患者真菌感染的可行性

The Feasibility of Ibrexafungerp for the Treatment of Fungal Infections in Patients with Hematological Malignancies.

作者信息

Daraskevicius Justinas, Petraitis Vidmantas, Davainis Linas, Zucenka Andrius

机构信息

Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania.

Department of Medicine, Division of Infectious Diseases, Transplantation-Oncology Infectious Diseases Program, Weill Cornell Medicine of Cornell University, New York, NY 10065, USA.

出版信息

J Fungi (Basel). 2022 Apr 23;8(5):440. doi: 10.3390/jof8050440.

Abstract

Invasive fungal diseases (IFD) remain a major cause of morbidity and mortality in hematological patients, especially those undergoing hematopoietic stem cell transplantation (HSCT). Despite relatively high incidence, diagnosis and treatment remain a challenge due to non-specific manifestation and limited antifungal armamentarium. A first-in-class triterpenoid antifungal ibrexafungerp that acts by inhibiting the glucan synthase enzyme in the fungal cell wall was recently approved by the USA Food and Drug Administration for the treatment of vaginal yeast infections. Preclinical data show activity against numerous fungi species, including azole- and echinocandin-resistant strains. Preliminary data from ongoing phase 3 studies in IFD have been encouraging, but the role of ibrexafungerp in hematological patients who develop fungal infections has not yet been described. Herein, we discuss the feasibility of oral ibrexafungerp-based antifungal therapy for adult patients with hematological malignancies who have either undergone HSCT or received treatment with a novel targeted therapy agent. We present four clinical cases where ibrexafungerp alone or in combination with other antifungal agents was successfully employed for the management of refractory fungal infection. We describe real-life experiences showing the potential clinical implementation of ibrexafungerp for patients with hematological malignancies for the first time, and provoke future discussion.

摘要

侵袭性真菌病(IFD)仍然是血液系统疾病患者发病和死亡的主要原因,尤其是那些接受造血干细胞移植(HSCT)的患者。尽管发病率相对较高,但由于临床表现不特异且抗真菌药物有限,诊断和治疗仍然是一项挑战。一种通过抑制真菌细胞壁中的葡聚糖合酶发挥作用的一流三萜类抗真菌药物ibrexafungerp最近被美国食品药品监督管理局批准用于治疗阴道酵母菌感染。临床前数据显示其对多种真菌具有活性,包括对唑类和棘白菌素耐药的菌株。IFD正在进行的3期研究的初步数据令人鼓舞,但ibrexafungerp在发生真菌感染的血液系统疾病患者中的作用尚未见描述。在此,我们讨论了对于接受过HSCT或接受过新型靶向治疗药物治疗的血液系统恶性肿瘤成年患者,基于口服ibrexafungerp的抗真菌治疗的可行性。我们展示了4例临床病例,其中ibrexafungerp单独或与其他抗真菌药物联合成功用于难治性真菌感染的治疗。我们首次描述了显示ibrexafungerp在血液系统恶性肿瘤患者中潜在临床应用的实际经验,并引发未来的讨论。

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